AU2003240331B2 - ACE2 activation for treatment of heart, lung and kidney disease and hypertension - Google Patents
ACE2 activation for treatment of heart, lung and kidney disease and hypertension Download PDFInfo
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- AU2003240331B2 AU2003240331B2 AU2003240331A AU2003240331A AU2003240331B2 AU 2003240331 B2 AU2003240331 B2 AU 2003240331B2 AU 2003240331 A AU2003240331 A AU 2003240331A AU 2003240331 A AU2003240331 A AU 2003240331A AU 2003240331 B2 AU2003240331 B2 AU 2003240331B2
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| AU2007325761A1 (en) * | 2006-11-22 | 2008-06-05 | University Of Florida Research Foundation, Inc. | ACE2 activator compounds and methods of use thereof |
| AT505262A1 (de) | 2007-06-12 | 2008-12-15 | Apeiron Biolog Forschungs Und | Rekombinantes ace2 polypeptid |
| AT506258A1 (de) | 2007-12-18 | 2009-07-15 | Apeiron Biolog Forschungs Und | Behandlung inflammatorischer krankheiten |
| EP2077119A1 (de) | 2007-12-21 | 2009-07-08 | Apeiron Biologics Forschungs- und Entwicklungsgesellschaft M.B.H. | Behandlung von Fibrosen und Lebererkrankungen |
| AT506632A1 (de) * | 2008-04-09 | 2009-10-15 | Apeiron Biolog Forschungs Und | Behandlung von tumorerkrankungen |
| CA2957211C (en) | 2013-10-18 | 2022-07-05 | Trustees Of The University Of Pennsylvania | Oral delivery of angiotensin converting enzyme 2 (ace2) or angiotensin-(1-7) bioencapsulated in plant cells |
| EP3717077A1 (en) | 2017-11-29 | 2020-10-07 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft | Methods for modulating pigmentation by angiotensin-converting enzyme 2 modulation |
| MX2020007071A (es) | 2018-01-05 | 2020-11-11 | Platelet Biogenesis Inc | Composiciones y metodos para producir megacariocitos. |
| CN108660205A (zh) * | 2018-07-04 | 2018-10-16 | 刘城 | 一种糖尿病遗传风险评估试剂盒及其运用 |
| CN110577588B (zh) * | 2019-09-29 | 2020-12-29 | 苏州大学 | 一种凹耳蛙免疫调节肽及其应用 |
| CN111087445B (zh) * | 2019-10-14 | 2021-08-24 | 浙江大学 | 一种用于ace2活性检测的质谱探针及其制备方法和应用 |
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| US20240002935A1 (en) * | 2020-04-11 | 2024-01-04 | Geneticure Inc. | Genetic method for diagnosis and treatment of pre and post coronavirus infections |
| WO2022008642A1 (en) | 2020-07-08 | 2022-01-13 | Apeiron Biologics Ag | Treatment of sars-cov-2 infection with a combination of targets |
| JP7563940B2 (ja) * | 2020-10-22 | 2024-10-08 | シスメックス株式会社 | 呼吸器感染症に関する情報の取得方法、バイオマーカーの測定値のモニタリング方法、試薬キット、呼吸器感染症に関する情報の取得装置及びコンピュータプログラム |
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| US20240358008A1 (en) * | 2021-08-31 | 2024-10-31 | New York University | COMPOSITIONS AND METHODS FOR SWITCHING ANTIBIOTIC RESISTANCE MARKERS PROGRESSIVELY FOR INTEGRATION (mSwAP-In) |
| EP4147702A1 (en) | 2021-09-13 | 2023-03-15 | Medizinische Universität Graz | Novel combination of heparin and ace2 decoys for the treatment of covid-19 |
| WO2023102156A1 (en) | 2021-12-03 | 2023-06-08 | Wisconsin Alumni Research Foundation | Mutant ace2 proteins and methods of using same |
| WO2023144625A2 (en) * | 2022-01-27 | 2023-08-03 | The Chinese University Of Hong Kong | Enhanced hace2-based neutralizing agents against sars-cov-2 infection |
Citations (1)
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|---|---|---|---|---|
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Family Cites Families (33)
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| JP4520569B2 (ja) | 2000-02-18 | 2010-08-04 | 照彦 豊岡 | 拡張型心筋症の遺伝子治療剤 |
| US6303830B1 (en) * | 2000-03-15 | 2001-10-16 | Union Carbide Chemicals & Plastics Technology Corporation | Metal-ligand complex catalyzed processes |
| PT1515752E (pt) * | 2002-06-19 | 2009-03-05 | Univ Health Network | Activação de ace2 para o tratamento de doença cardíaca, pulmonar e renal e de hipertensão |
-
2003
- 2003-06-19 PT PT03729747T patent/PT1515752E/pt unknown
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- 2003-06-19 CN CN038183595A patent/CN1671425B/zh not_active Expired - Lifetime
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- 2003-06-19 EP EP03729747A patent/EP1515752B1/en not_active Expired - Lifetime
- 2003-06-19 WO PCT/CA2003/000882 patent/WO2004000367A1/en active Application Filing
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2009
- 2009-02-26 CY CY20091100214T patent/CY1108829T1/el unknown
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2010
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002012471A2 (en) * | 2000-08-09 | 2002-02-14 | Millennium Pharmaceuticals, Inc. | Angiotensin converting enzyme homolog and uses therefor |
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| ES2424971T3 (es) | 2013-10-10 |
| US7794707B2 (en) | 2010-09-14 |
| US8802084B2 (en) | 2014-08-12 |
| PT2332582E (pt) | 2014-01-28 |
| EP2332582A1 (en) | 2011-06-15 |
| PT1515752E (pt) | 2009-03-05 |
| CA2489873A1 (en) | 2003-12-31 |
| DK1515752T3 (da) | 2009-03-23 |
| JP2006504637A (ja) | 2006-02-09 |
| DE60324925D1 (de) | 2009-01-08 |
| SI1515752T1 (sl) | 2009-06-30 |
| CN1671425B (zh) | 2013-07-10 |
| ATE415175T1 (de) | 2008-12-15 |
| ES2443305T3 (es) | 2014-02-18 |
| US20100311822A1 (en) | 2010-12-09 |
| DK2332582T3 (da) | 2014-01-20 |
| US20050251873A1 (en) | 2005-11-10 |
| EP2047867A1 (en) | 2009-04-15 |
| EP2047867B1 (en) | 2013-05-22 |
| SI2332582T1 (sl) | 2014-03-31 |
| CN101961493A (zh) | 2011-02-02 |
| CN1671425A (zh) | 2005-09-21 |
| US20120251520A1 (en) | 2012-10-04 |
| CY1108829T1 (el) | 2014-04-09 |
| WO2004000367A1 (en) | 2003-12-31 |
| ES2318137T3 (es) | 2009-05-01 |
| EP1515752A1 (en) | 2005-03-23 |
| US8211426B2 (en) | 2012-07-03 |
| CA2489873C (en) | 2016-08-09 |
| EP1515752B1 (en) | 2008-11-26 |
| AU2003240331A1 (en) | 2004-01-06 |
| EP2332582B1 (en) | 2013-10-30 |
| JP4598518B2 (ja) | 2010-12-15 |
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